Higher-Order Thalamic Input to Primary Sensory Cortex

项目总结/摘要 高级（HO）丘脑核团构成了丘脑的大部分[5]，最近开始被研究。 被认为是早期感觉处理的重要贡献者[1，6，8，9，13，16]，但他们对初级感觉处理的输入 我们对感觉皮层还不太了解。HO核含有异质神经元亚群， 差异连接，模糊了我们对它们传输的信息以及这些信息如何传输的理解。 参与皮层处理的各个阶段。在躯体感觉系统中，后内侧核 (POm)已知接收皮层和皮层下信息[4，5，14]，但不知道哪些输入 驱动活动的POm神经元投射到S1，也没有这个电路如何影响S1活动。在类似的HO 视觉通路，Pulvinar（Pulv）也协调皮质区之间的通信[1，6]，并接收亚- 来自上级丘的皮质输入[5]。类似地，尽管已知Pulv对加工中的贡献， V1 [8，9]，目前尚不清楚是哪些区域驱动Pulv投影到V1，也不知道该途径如何影响V1中的目标。 所提出的实验旨在通过交叉解剖和 生理方法，映射和表征HO丘脑核的突触输入和输出， 小鼠该分析将采用新开发的亚群特异性病毒策略[25，26]， 荧光报告基因和光遗传学探针，与 体外细胞内记录，这将阐明哪些区域驱动HO细胞投射到原发灶的活动。 皮质，这些输入如何协调，以及HO投射是否驱动或调节S1和V1的反应。 虽然这两个回路中的每一个都对理解感官中的信息处理感兴趣， 系统，这两个系统都是研究系统神经科学的中心平台，这个项目将比较 在两种感觉方式，提供了一种方法来比较/对比功能的潜在模式， 连通性。已知HO丘脑核有几个共同的特征[4，5]，HO（但不是FO） 在精神分裂症患者中，细胞核萎缩，神经元减少[17-19]。目前的提议是调查 HO丘脑输入到初级感觉皮层的性质和组织都将提供对丘脑的深入了解， 皮层关系在早期感觉处理以及阐明电路水平的机制， 在精神分裂症和其他疾病状态下出现的缺陷。 数据也将是有用的，在指导未来在体内分析相同的电路。主要培训目标 这项建议的重点是学习如何使用电路特定的光遗传学技术沿着与盟军的技能， 协助设计和执行连接细胞，电路和感觉系统的神经科学实验， 帮助我成为一名独立的研究者。

PROJECT SUMMARY / ABSTRACT Higher-order (HO) thalamic nuclei make up most of the thalamus [5], and have recently begun to be appreciated as important contributors to early sensory processing [1,6,8,9,13,16], but their inputs to primary sensory cortex are not well understood. HO nuclei contain heterogeneous neuronal sub-populations with differential connectivity, clouding our understanding of the messages they transmit and how these messages contribute to each stage of cortical processing. In the somatosensory system, the Posterior Medial nucleus (POm) is known to receive both cortical and sub-cortical information [4,5,14], but it is not known which inputs drive activity in POm neurons projecting to S1, nor how this circuit affects S1 activity. In the analogous HO visual pathway, Pulvinar (Pulv) also coordinates communication between cortical areas [1,6], and receives sub- cortical input from the Superior Colliculus [5]. Similarly, despite known contributions of Pulv to processing in V1 [8,9], it is not known what areas drive the Pulv projection to V1 nor how this pathway affects targets in V1. The proposed experiments aim to dissect these circuits by means of an intersectional anatomical and physiological approach, mapping and characterizing synaptic inputs and outputs of the HO thalamic nuclei of mice. This analysis will employ newly developed, sub-population-specific viral strategies [25,26] to deliver fluorescent reporters and optogenetic probes to the projection groups in question, in combination with intracellular recordings in vitro that will clarify what areas are driving activity in HO cells projecting to primary cortex, how these inputs coordinate, and whether HO projections drive or modulate responses in S1 and V1. While each of these two circuits alone is of interest to understanding information processing in sensory systems, and both systems are central platforms for studying systems neuroscience, this project will compare across both sensory modalities, providing a way to compare/contrast the underlying patterns of functional connectivity. HO thalamic nuclei are known to have several features in common [4,5], and HO (but not FO) nuclei are shrunken with fewer neurons in schizophrenic patients [17-19]. The current proposal to probe the nature and organization of HO thalamic input to primary sensory cortex will both provide insight into thalamo- cortical relationships in early sensory processing as well as elucidate circuit-level mechanisms that may underlie deficits seen in schizophrenia and other disease states. Data will also be useful in guiding future in vivo analyses of the same circuits. The major training goal of this proposal is to learn how to use circuit-specific optogenetics techniques along with allied skills that will assist in designing and executing neuroscience experiments that bridge cells, circuits, and sensory systems, and help me develop as an independent researcher.